BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the ...BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.展开更多
肾脏疾病在当前临床背景下的发病率很高,其中慢性肾病矿物质与骨骼疾病(chronic kidney diseasemineral and bone disorder,CKD-MBD)是慢性肾脏疾病的常见并发症,发病率也比较高,会使得甲状旁腺素或钙、磷等元素出现异常代谢情况,骨代...肾脏疾病在当前临床背景下的发病率很高,其中慢性肾病矿物质与骨骼疾病(chronic kidney diseasemineral and bone disorder,CKD-MBD)是慢性肾脏疾病的常见并发症,发病率也比较高,会使得甲状旁腺素或钙、磷等元素出现异常代谢情况,骨代谢指标出现异常,造成血管等组织钙化问题。CKD-MBD的出现将严重影响患者的骨组织代谢,长期则会干扰远期生存质量。对此,研究CKD-MBD病理生理过程中的信号调控机制,在临床和生物学领域备受关注,也是近几年研究的热点问题之一。而过往的临床研究实践表明,Wnt/β-catenin信号通路在此病的发生中发挥很重要的作用,同时也影响肾间质纤维化的发展。这一信号通路中,Klotho-FGF23轴十分关键,负责调控该信号通路的发生、发展。Klotho-FGF23轴中,FGF23代表着成纤维细胞因子23,本质是一种蛋白质,主要在骨细胞中合成,该因子主要是参与钙、磷代谢调节工作,Klotho代表一种共受体,本质也是一种蛋白质,而且是单次跨膜蛋白质,两者结合到一起将直接作用到肾脏和甲状旁腺,因此发挥代谢调节作用。在医学研究的不断深入下,Klotho-FGF23轴调控的Wnt/β-catenin信号通路,可能会成为新时期治疗此病的新靶点。基于此,本次就立足于当前研究所得,探究上述调控过程的发展变化。展开更多
文摘BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.
文摘目的:观察益肾方对腺嘌呤所致的慢性肾衰竭早期大鼠血清FGF23和肾组织Klotho mRNA值表达的影响,从而探讨益肾方延缓慢性肾衰竭进展的作用机制。方法:90只大鼠随机分为空白组、模型组、尿毒清组和益肾方低、中、高剂量(0.675、1.35、2.7 g/kg)组,每组各15只;除空白组外,其余各组采用腺嘌呤(200 mg·kg^(-1)·d^(-1))灌胃4周造模,造模成功后,除空白组和模型组外,其余各组给药干预8周。测定Scr、BUN、UmAlb、24 h UTP;HE、Masson染色镜下观察大鼠肾组织的病理变化;用ELISA检测血清FGF23蛋白含量、RT-PCR法检测肾组织Klotho mRNA的表达。结果:给药8周后,与模型组相比较,尿毒清组和益肾方组Scr、BUN、24 h UTP、UmAlb水平降低(P<0.05),血清FGF23的表达量均有下降(P<0.05),益肾方高剂量组下降更为明显(P<0.05),肾组织Klotho mRNA表达量增多,以益肾方高剂量组增加的更明显(P<0.05)。结论:益肾方能明显延缓慢性肾衰竭早期大鼠的进展,其作用机制可能与Klotho/FGF23轴有关。
文摘肾脏疾病在当前临床背景下的发病率很高,其中慢性肾病矿物质与骨骼疾病(chronic kidney diseasemineral and bone disorder,CKD-MBD)是慢性肾脏疾病的常见并发症,发病率也比较高,会使得甲状旁腺素或钙、磷等元素出现异常代谢情况,骨代谢指标出现异常,造成血管等组织钙化问题。CKD-MBD的出现将严重影响患者的骨组织代谢,长期则会干扰远期生存质量。对此,研究CKD-MBD病理生理过程中的信号调控机制,在临床和生物学领域备受关注,也是近几年研究的热点问题之一。而过往的临床研究实践表明,Wnt/β-catenin信号通路在此病的发生中发挥很重要的作用,同时也影响肾间质纤维化的发展。这一信号通路中,Klotho-FGF23轴十分关键,负责调控该信号通路的发生、发展。Klotho-FGF23轴中,FGF23代表着成纤维细胞因子23,本质是一种蛋白质,主要在骨细胞中合成,该因子主要是参与钙、磷代谢调节工作,Klotho代表一种共受体,本质也是一种蛋白质,而且是单次跨膜蛋白质,两者结合到一起将直接作用到肾脏和甲状旁腺,因此发挥代谢调节作用。在医学研究的不断深入下,Klotho-FGF23轴调控的Wnt/β-catenin信号通路,可能会成为新时期治疗此病的新靶点。基于此,本次就立足于当前研究所得,探究上述调控过程的发展变化。
